Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation

• Prenatal nicotine exposure elevated maternal and fetal blood glucocorticoid level.
• Maternal and fetal metabonomes were altered due to prenatal nicotine exposure.
• Metabonomic alterations in biofluids were associated with glucocorticoid elevation.
• Some potential biomarkers in maternal plasma may alert nicotine-induced IUGR.

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11–20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using 1H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r = 0.356, n = 32, P < 0.05), while there was a negative correlation between fetal (r = −0.639, n = 32, P < 0.01) and maternal (r = −0.530, n = 32, P < 0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine.